RESUMEN
BACKGROUND: There is a risk of terror attacks in the Federal Republic of Germany, which might increase in the future. A timely comprehensive strategy for treatment and care of a large number of casualties helps minimize chaos and improve the outcome of patients. Adequate training is vital for successful implementation of an emergency plan. Therefore, the effectiveness of training should be assessed and evaluated; however, data collection capabilities for training events are extremely limited, so that publications on the topic are almost impossible to find. OBJECTIVE: This study aimed to collect data from a simulated terrorist attack in order to draw conclusions from a clinical point of view concerning the improvement of preclinical and clinical management, taking interface problems into consideration. MATERIAL AND METHODS: On 19 October 2019 the Ministry of the Interior, Digitalization and Migration of Baden-Württemberg conducted a large-scale simulation of a terrorist attack in the city center of Constance, called the Baden-Württemberg counterterrorism exercise (BWTEX). The simulation included an explosion of a car bomb as well as the use of firearms by terrorists. The large scale of the simulation with the high number of participants in combination with close cooperation between military and civil forces was unprecedented. The police force, the armed forces, civil protection forces, air rescue teams and staff from Constance, Friedrichshafen and Sigmaringen regional hospitals in southwest Germany worked together to treat simulated injuries to victims of the attack. The following parameters were recorded when the injured patients arrived at the hospital: prehospital triage time, prehospital triage score, initial treatment and quality of documentation on site as well as triage time, triage score, injury severity scale (ISS) score based on the specified injury pattern, treatment, and quality of documentation on hospital arrival. RESULTS: Out of a total of 84 "injured patients" 55 were admitted to hospital and 80% were triaged at the scene. Injured patients of triage category 1 (TK1 red: life-threatening injury, immediate treatment) arrived at the hospital 198⯱ 50â¯min after the attack, injured patients of triage category 2 (TK2 yellow: severely injured, urgent treatment) after 131⯱ 44â¯min and injured patients of triage category 3 (TK3 green: slightly injured, non-urgent treatment) arrived after 157⯱ 46â¯min. There was no significant difference in terms of arrival time at the hospital between the triage scores (râ¯= 0.2) or between the ISS scores (râ¯= 0.43). The authors assume that approximately 44% of TK1 patients would have died due to avoidable time delays. Prehospital medical documentation was insufficient in 78% and insufficient in 65% in the hospitals. CONCLUSION: A mass casualty incident resulting from a terrorist attack differs greatly from a conventional mass casualty incident. The scene of the attack has to be evacuated as quickly as possible, which means that a large number of patients arrive untreated at the nearest hospitals. The setting up of treatment facilities in city centers and areas close to the city seems to be counterproductive because the time delay may result in higher mortality rates of victims. The particularities of mass casualties caused by a terrorist attack have to be incorporated into terrorist attack training.
Asunto(s)
Planificación en Desastres/métodos , Servicios Médicos de Urgencia/organización & administración , Triaje/métodos , Servicio de Urgencia en Hospital/organización & administración , Alemania , Hospitalización , Hospitales , Humanos , Incidentes con Víctimas en Masa , Entrenamiento Simulado , TerrorismoRESUMEN
BACKGROUND: Since the advent of democracy, the South African government has been putting charters, policies, strategies and plans in place in an effort to strengthen public health system performance and enhance service delivery. However, public health programme performance and outcomes remained poor while the burden of disease increased. This was also the case in the Free State Province, where major public health system challenges occurred around 2012. Assessment was necessary in order to inform health system strengthening. METHODS: The study entailed a multi-method situation appraisal utilising information collated in 44 reports generated in 2013 through presentations by unit managers, subdistrict assessments by district clinical specialist teams, and group discussions with district managers, clinic supervisors, primary health care managers and chief executive and clinical officers of hospitals. These data were validated through community and provincial health indabas including non-governmental organisations, councils and academics, as well as unannounced facility visits involving discussions with a wide range of functionaries and patients. The reports were reviewed using the World Health Organization health system building blocks as a priori themes with subsequent identification of emerging subthemes. Data from the different methods employed were triangulated in a causal loop diagram showing the complex interactions between the components of an (in) effective health system. RESULTS: The major subthemes or challenges that emerged under each a priori theme included: firstly, under the 'service delivery' a priori theme, 'fragmentation of health services' (42 reports); secondly, under the 'health workforce' a priori theme, 'staff shortages' (39 reports); thirdly, under the 'health financing' a priori theme, 'financial/cash-flow problems' (39 reports); fourthly, under the 'leadership and governance' a priori theme, 'risk to patient care' (38 reports); fifthly, under the 'medical products/technologies' a priori theme, 'dysfunctional communication technology' (27 reports); and, sixthly, under the 'information' a priori theme, 'poor information management' (26 reports). CONCLUSION: The major overall public health system challenges reported by stakeholders involved fragmentation of services, staff shortages and financial/cash-flow problems. In order to effect health systems strengthening there was particularly a need to improve integration and address human and financial deficiencies in this setting.
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Atención a la Salud/organización & administración , Democracia , Salud Pública , Investigación sobre Servicios de Salud , Humanos , SudáfricaRESUMEN
The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ßlactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).
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Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Programas de Optimización del Uso de los Antimicrobianos , Biomarcadores , Monitoreo de Drogas , Humanos , Unidades de Cuidados Intensivos , Choque Séptico/tratamiento farmacológico , beta-Lactamas/farmacocinética , beta-Lactamas/uso terapéuticoRESUMEN
In January 2018 the recent revision of the S2k guidelines on calculated parenteral initial treatment of bacterial diseases in adults-update 2018 (Editor: Paul Ehrlich Society for Chemotherapy, PEG) was realized. It is a helpful tool for the complex infectious disease setting in an intensive care unit. The present summary of the guidelines focuses on the topics of anti-infective agents, including new substances, pharmacokinetics and pharmacodynamics as well as on microbiology, resistance development and recommendations for calculated drug therapy in septic patients. As in past revisions the recent resistance situation and results of new clinical studies are considered and anti-infective agents are summarized in a table.
Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Guías como Asunto , Humanos , Infusiones ParenteralesRESUMEN
Sepsis-induced changes in pharmacokinetic parameters are a well-known problem in intensive care medicine. Dosing of antibiotics in this setting is therefore challenging. Alterations to the substance-specific kinetics of anti-infective substances have an effect on the distribution and excretion processes in the body. Increased clearance and an increased distribution volume (Vd) and particularly compromized organ function with reduced antibiotic elimination are often encountered in patients with sepsis. Renal replacement treatment, which is frequently used in intensive care medicine, represents a substantial intervention in this system. Current international guidelines recommend individualized dosing strategies and adaptation of doses according to measured serum levels and pharmacokinetic/pharmacodynamic (PK/PD) parameters as concepts to optimize anti-infective therapy in the critically ill. Likewise, the recommendation to adjust the administration form of beta-lactam antibiotics to prolonged or continuous infusion can be found increasingly more often in the literature. This article reviews the background of the individual dosing in intensive care patients and their applicability to the clinical routine.
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Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/farmacocinética , Cuidados Críticos , Monitoreo de Drogas , Humanos , Medicina de Precisión , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Choque Séptico/tratamiento farmacológicoRESUMEN
INTRODUCTION: To determine whether the current set of evaluation criteria used for dilute Russel Viper Venom Time (dRVVT) investigations in the routine laboratory meet expectation and identify possible shortcomings. METHODS: All dRVVT assays requested from January 2015 to December 2015 were appraised in this cross-sectional study. The raw data panels were compared with the new reference interval, established in 2016, to determine the sequence of assays that should have been performed. The interpretive comments were audited, and false-negative reports identified. Interpretive comments according to three interpretation guidelines were compared. The reagent cost per assay was determined, and reagent cost wastage, due to redundant tests, was calculated. RESULTS: Only ~9% of dRVVT results authorized during 2015 had an interpretive comment included in the report. ~15% of these results were false-negative interpretations. There is a significant statistical difference in interpretive comments between the three interpretation methods. Redundant mixing tests resulted in R 7477.91 (~11%) reagent cost wastage in 2015. CONCLUSIONS: We managed to demonstrate very evident deficiencies in our own practice and managed to establish a standardized workflow that will potentially render our service more efficient and cost effective, aiding clinicians in making improved treatment decisions and diagnoses. Furthermore, it is essential that standard operating procedures be kept up to date and executed by all staff in the laboratory.
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Hematología/métodos , Tiempo de Protrombina/normas , Pruebas de Coagulación Sanguínea , Estudios Transversales , Reacciones Falso Negativas , Humanos , Guías de Práctica Clínica como Asunto , Tiempo de Protrombina/economía , Flujo de TrabajoRESUMEN
Pharmacokinetic variability of anti-infective drugs due to pathophysiological changes by severe sepsis and septic shock is a well-known problem for critically ill patients resulting in suboptimal serum and most likely tissue concentrations of these agents.To cover a wide range of potential pathogens, high concentrations of broad spectrum anti-infectives have to reach the site of infection. Microbiological susceptibility testing (susceptible, intermediate, resistant) don't take the pharmacokinetic variability into account and are based on data generated by non-critically ill patients. But inter-patient variability in distribution and elimination of anti-infective drugs in ICU patients is extremely high and also highly unpredictable. Drug clearance of mainly renally eliminated drugs and thus the required dose can differ up to 10-fold due to the variability in renal function in patients with severe infections. To assure a timely and adequate anti-infective regime, individual dosing and therapeutic drug monitoring (TDM) seem to be appropriate tools in the setting of pathophysiological changes in pharmacokinetics (PK) and pharmakodynamics (PD) due to severe sepsis. In the case of known minimal inhibitory concentration, PK/PD indices (time or peak concentration dependent activity) and measured serum level can provide an optimal target concentration for the individual drug and patient.Modern anti-infective management for ICU patients includes more than the choice of drug and prompt application. Individual dosing, optimized prolonged infusion time and TDM give way to new and promising opportunities in infection control.
Asunto(s)
Antibacterianos , Monitoreo de Drogas , Sepsis , Choque Séptico , Antibacterianos/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Sepsis/tratamiento farmacológico , Choque Séptico/tratamiento farmacológicoRESUMEN
The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Farmacorresistencia Bacteriana , Humanos , Unidades de Cuidados Intensivos , Sepsis/microbiología , Sepsis/mortalidad , Choque Séptico/diagnóstico , Choque Séptico/tratamiento farmacológicoRESUMEN
Cysteamine is a small aminothiol endogenously derived from coenzyme A degradation. For some decades, synthetic cysteamine has been employed for the treatment of cystinosis, and new uses of the drug continue to emerge. In this review, we discuss the role of cysteamine in cellular and extracellular homeostasis and focus on the potential use of aminothiols to reconstitute the function of proteins harboring arginine (Arg) to cysteine (Cys) mutations, via repair of the Cys residue into a moiety that introduces an amino group, as seen in basic amino acid residues Lys and Arg. Cysteamine has been utilized in vitro and ex vivo in four different genetic disorders, and thus provides "proof of principle" that aminothiols can modify Cys residues. Other aminothiols such as mercaptoethylguanidine (MEG) with closer structural resemblance to the guanidinium moiety of Arg are under examination for their predicted enhanced capacity to reconstitute loss of function. Although the use of aminothiols holds clinical potential, more studies are required to refine specificity and treatment design. The efficacy of aminothiols to target proteins may vary substantially depending on their specific extracellular and intracellular locations. Redox potential, pH, and specific aminothiol abundance in each physiological compartment are expected to influence the reactivity and turnover of cysteamine and analogous drugs. Upcoming research will require the use of suitable cell and animal models featuring Arg to Cys mutations. Since, in general, Arg to Cys changes comprise about 8% of missense mutations, repair of this specific mutation may provide promising avenues for many genetic diseases.
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Arginina/química , Cisteamina/química , Cisteína/química , Cistinosis/terapia , Mutación , Animales , Apolipoproteína E3/metabolismo , Argininosuccinatoliasa/metabolismo , Cistationina betasintasa/metabolismo , Cistinosis/genética , Cistinosis/metabolismo , Homeostasis , Humanos , Concentración de Iones de Hidrógeno , Conformación Molecular , Mutación Missense , Oxidación-Reducción , Compuestos de Sulfhidrilo/química , Tromboplastina/metabolismoRESUMEN
Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel.
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Quimioterapia de Inducción , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/terapia , Paclitaxel/administración & dosificación , Terapia Recuperativa , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: South Africa has the second worst tuberculosis-human immunodeficiency virus (TB-HIV) syndemic in the world: in 2011, the TB-HIV co-infection rate was estimated at 65%. Integration of TB and HIV health-care services was implemented to increase antiretroviral treatment (ART) uptake among eligible patients. AIM: To evaluate whether integrated TB and HIV facilities had better ART uptake among eligible patients compared to non-integrated facilities. METHODS: A cross-sectional study using routine TB programme data from January to December 2010. ART eligibility was defined as a CD4+ cell count <350 cells/µl. RESULTS: Respectively 2761 (86.8%) and 3611 (84.7%) patients were eligible for ART at integrated and non-integrated facilities (P < 0.001). The proportion of patients started on ART at integrated facilities did not differ significantly from that of non-integrated facilities (35.9% vs. 37.1%, P = 0.340), but the proportion with unknown HIV status (31.8% vs. 24.5%, P < 0.001) and unknown CD4+ cell count (40.9% vs. 30.4%, P < 0.001) did. CONCLUSION: Integration of TB and HIV services in the Free State (2009-2010) was not associated with improved ART uptake. The reasons why are not clear. Of concern are the high proportions of unknown HIV status and CD4+ cell count results, especially at integrated facilities, and the small proportion of patients on ART, which may indicate poor implementation of integration.
Contexte : L'Afrique du Sud est au deuxième rang dans le monde de la « syndémie ¼ tuberculose/virus d'immunodéficience humaine (TB-VIH) : en 2011, le taux de coïnfection TB-VIH a été estimé à 65%. L'intégration des services de soins de la TB et du VIH a été mise en Åuvre pour augmenter la mise sous traitement antirétroviral (ART) chez les patients éligibles.Objectif : Evaluer si les structures intégrant TB et VIH comparées aux structures non-intégrées ont un meilleur taux de prise d'ART parmi les patients éligibles.Méthodes : Etude transversale utilisant les données de routine des programmes TB de janvier à décembre 2010. L'éligibilité à l'ART a été définie comme un comptage de CD4+ <350 cellules/µl.Résultats : Respectivement 2761 (86,8%) et 3611 (84,7%) patients ont été éligibles pour l'ART dans les structures intégrées et non-intégrées (P < 0,001). La proportion de patients mis sous ART dans des structures intégrées comparées aux structures non-intégrées n'a pas été significativement différente (35,9% contre 37,1%; P = 0,340); par contre, la différence a été significative pour les patients de statut VIH inconnu (31,8% contre 24,5%; P < 0,001) et de comptage de CD4+ inconnu (40,9% contre 30,4%; P < 0,001).Conclusion : L'intégration des services de TB et VIH dans le Free State (20092010) n'a pas été associée à une amélioration de la prise de l'ART. Les raisons n'en sont pas très claires. Par contre, il est préoccupant de constater la proportion élevée de statut VIH inconnu et d'absence de résultats de comptage des CD4+, surtout dans les structures intégrées, et la faible proportion de patients sous ART, qui témoigne d'une mise en Åuvre médiocre de l'intégration.
Marco de referencia: Suráfrica ocupa el segundo puesto de los países con la más alta sindemia de tuberculosis (TB) e infección por el virus de la inmunodeficiencia humana (VIH) en todo el mundo. Se estimó que en el 2011 la tasa de coinfección por el VIH y la TB fue 65%. Se integraron los servicios de atención de la TB y el VIH con el propósito de fomentar la aceptación del tratamiento antirretrovírico (ART) por parte de los pacientes que reúnen las condiciones para recibirlo.Objetivo: Comparar la utilización del ART en los centros integrados de atención de la TB y VIH y en centros no integrados.Método: Se llevó a cabo un estudio transversal de los datos sistemáticos del programa contra la TB de enero a diciembre del 2010. El criterio de inclusión al ART fue un recuento de linfocitos CD4+ <350 células/µl.Resultados: En los centros de atención integrada se encontraron 2761 pacientes aptos al ART (86,8%) y 3611 en los centros no integrados (84,7%) (P < 0,001). La diferencia en la proporción de pacientes que comenzó el tratamiento no fue estadísticamente significativa (35,9% contra 37,1%; P = 0,340); se observó una diferencia significativa en el porcentaje de pacientes que desconocía su situación frente al VIH (31,8% en los centros integrados contra 24,5% en los demás centros; P < 0,001) y en la proporción de pacientes VIH cuyos resultados del recuento de linfocitos CD4+ se desconocía (40,9% contra 30,4%; P < 0,001).Conclusión: La integración de los servicios de atención de la TB y la VIH en la Provincia del Estado Libre de Suráfrica (del 2009 al 2010) no se asoció con una mayor utilización del ART y las razones de este resultado no son claras. Son fuente de inquietud la alta proporción de pacientes que desconocen su situación frente al VIH y la falta de resultados del recuento de linfocitos CD4+, sobre todo en los centros de atención integrada y la baja proporción de pacientes que recibe ART; esta situación puede obedecer a una deficiencia en la integración de los servicios.
RESUMEN
Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.
Asunto(s)
Busulfano/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Satisfacción del Paciente , Acondicionamiento Pretrasplante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Actitud del Personal de Salud , Busulfano/farmacocinética , Atención a la Salud/métodos , Atención a la Salud/organización & administración , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Acondicionamiento Pretrasplante/efectos adversos , Trasplante HomólogoRESUMEN
BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. METHODS: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. RESULTS: Three-year OS was 20% (s.e.±8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s.e.±10%) and 11% (s.e.±6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. CONCLUSION: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Rabdomiosarcoma/cirugía , Adolescente , Adulto , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Rabdomiosarcoma/mortalidad , Trasplante Homólogo , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Albuminuria is an important biomarker of renal dysfunction and is a major mediator of renal damage and fibrosis during kidney disease. The mechanisms underlying albumin-induced renal fibrosis remain unclear. There has been significant interest in γ-secretase activity in tubular epithelial cells in recent times; however, its potential role in albumin-induced fibrosis has not been investigated. EXPERIMENTAL APPROACH: The primary aim of this study was to examine the role of γ-secretase in albumin-induced fibrotic effects in proximal tubular cells. The effects of increasing albumin concentrations on fibrosis indicators and mediators in the human HK-2 cell line were examined in the presence and absence of a γ-secretase inhibitor, compound E. KEY RESULTS: Treatment with albumin resulted in a number of pro-fibrotic effects, including up-regulation of fibronectin, TGF-ß1 and the EGF-R. Interestingly, similar effects were observed in response to treatment with the γ-secretase inhibitor, compound E. Co-treatment of cells with albumin and an EGF-R inhibitor, AG-1478, resulted in significant inhibition of the observed pro-fibrotic effects, suggesting a major role for the EGF-R in albumin-induced fibrotic events. Albumin-induced effects on the EGF-R appeared to be mediated through inhibition of γ-secretase activity and were dependent on ERK-MAPK signalling. CONCLUSIONS AND IMPLICATIONS: These results provide novel insights into the mechanisms of albumin-induced fibrotic effects in tubular epithelial cells, suggesting important roles for the γ-secretase and the EGF-R. These results suggest that the proposed use of γ-secretase inhibitors as anti-fibrotic agents requires further investigation.
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Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Endocitosis/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Túbulos Renales Proximales/efectos de los fármacos , Proteolisis/efectos de los fármacos , Albúmina Sérica Bovina/metabolismo , Urotelio/efectos de los fármacos , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Benzodiazepinonas/farmacología , Bovinos , Línea Celular , Medio de Cultivo Libre de Suero , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Fibronectinas/metabolismo , Fibrosis , Humanos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Zarigüeyas , Quinazolinas/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Tirfostinos/farmacología , Urotelio/metabolismo , Urotelio/patologíaRESUMEN
Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either 'empirical' or 'preemptive' antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.
Asunto(s)
Neoplasias Hematológicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Infecciones Oportunistas/diagnóstico , Hematología , Humanos , Enfermedades Pulmonares Fúngicas/complicaciones , Oncología Médica , Infecciones Oportunistas/complicacionesRESUMEN
BACKGROUND: We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. PATIENTS AND METHODS: From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. RESULTS: Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. CONCLUSIONS: Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.